Genetic survey of a large cohort of CMT patients from Turkey revealed equal frequencies of CMT1A duplication and HNPP deletion

B. Ozes, M. Sivaci, K. Akyuz, H. Durmus, F. Deymeer, P. Oflazoglu, Y. Parman, E. Battaloglu

CMT1A duplication is reported to account for 55% of all genetically defined CMT cases whereas deletion of the same region, causing HNPP type, can explain the genetic basis in 9.1% of these cases. In this study, we have summarized the results of genetic analyses in CMT patients that have been performed since 1993 in our laboratory. The cohort includes 1088 CMT patients from different regions of Turkey that are mostly referred to our genetics laboratory from Istanbul Medical School known to serve patients coming throughout the country. Analysis for the presence of the CMT1A duplication and HNPP deletion is achieved as the first step by PCR using the known STR sequences. Samples without these re-arrangements are than re-evaluated considering the possible mode of inheritance, the EMG findings, and presence of additional symptoms like vocal cord paralysis or scoliosis. Disease-causing genes have been identified in 380 (35%) of the cases. Among those, 37.1% were explained by CMT1A duplication and 40.8% by HNPP deletion. GJB1 was the most frequently mutated gene in our cohort with a frequency of 5.3% (20 cases) that was lower than that reported in other studies (10%). Eleven recessive families (2.9%) had SH3TC2 gene mutations reinforcing the suggestion that it might be the most frequently mutated gene in recessive CMT. For seventeen CMT genes, mutation could be identified in less than five families for each. In 65% of our patients we could not perform any mutation screening except that they tested negative for CMT1A duplication/HNPP deletion. Whole exome sequencing was performed for the 33 cases for whom duplication, deletion, and mutations in Cx32, MPZ, and PMP22 tested negative. Mutations in known CMT genes could not be identified in 20 individuals (60.6%) using this approach and further analyses are currently being performed in these families to identify novel CMT genes. Considering the outcomes of the WES data, our cohort suggests a higher heterogeneity for CMT disease compared to other reports. These results suggests requirement for different genetic strategies to determine the mutations/genes underlying pathogenesis in countries where recessive cases are common due to high incidence of consanguineous marriages.

Externe Organisation(en)
Boğaziçi University (BU), Istanbul University
Journal of the Peripheral Nervous System
Anzahl der Seiten
ÖFOS 2012
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